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Submitted on March 15, 2008
Accepted on April 25, 2008
From the Department of Medicine (R.F., N.B.S., M.A.W.), University of California, San Francisco; the Eccles Institute of Human Genetics (R.M.C.), University of Utah, Salt Lake City; the Veterans Affairs Medical Center (B.N., N.B.S., M.A.W.), San Francisco, Calif; and the Research Institute (W.S.B.), California Pacific Medical Center, San Francisco.
* To whom correspondence should be addressed. E-mail: rfarzanehfar{at}medicine.ucsf.edu.
Background—Telomere shortening has been proposed as a marker of biological aging. Whether leukocyte telomere length is associated with mortality among patients with stable coronary artery disease (CAD) is unknown.
Methods and Results—We measured leukocyte telomere length in 780 patients with stable CAD in a prospective cohort study. Participants were categorized by quartiles of telomere length. Hazard Ratios (HRs) and 95% confidence intervals were calculated for all-cause mortality, heart failure (HF) hospitalization, and cardiovascular (CV) events. After 4.4 years of follow-up there were 166 deaths. Compared with participants in the highest telomere length quartile, those in the lowest quartile were at increased risk of death (age-adjusted HR 1.8; 95% CI 1.2 to 2.9). After multivariate adjustment for clinical (HR 2.1; CI 1.3 to 3.3), inflammatory (HR 2.0; CI 1.2 to 3.2), and echocardiographic (HR 1.9; CI 1.0 to 3.5) risk factors, patients in the lowest quartile of telomere length remained at significantly increased risk of death compared to those in the highest quartile. Patients in the lowest quartile of telomere length were also at significantly increased risk of HF hospitalization (HR 2.6; CI 1.1 to 6.0) but not CV events (HR 1.7; CI 0.9 to 3.5).
Conclusions—Reduced leukocyte telomere length is associated with all-cause mortality in patients with stable CAD. The prognostic value of short telomeres in predicting death is not completely captured by existing clinical, inflammatory, and echocardiographic markers of risk.
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